Massive hemorrhage from acute gastric erosions (stress ulcers) remains a devastating complication in severely traumatized or postoperative patients. The development of such acute mucosal damage is usually a result of a reduction in the ability of the mucosa to withstand intraluminal acid rather than hypersecretion of acid. Previous studies have shown that gastric mucosa normally protects itself against acid injury by (1) maintaining a permeability barrier to intraluminal H ions and (2) its ability to dispose of or to buffer the influxing H ions. Recently, gastric mucosa has been shown to actively secrete bicarbonate (HCO3 minus) into the lumen. This observation leads to a hypothesis that active secretion of HCO3 minus may be another important cytoprotective mechanism of the gastric mucosa, since the secreted HCO3 minus is likely to neutralize the intraluminal acid at the mucosal surface. To assess this hypothesis, the proposed studies are designed (1) to evaluate the role of HCO3 minus secretion on the acid-base status of the mucosa by measuring intramural pH and (2) to examine the changes in the rate of HCO3 minus secretion following various stimuli. They include (1) acetylsalicylic acid, a known gastric irritant, (2) Prostaglandin E2, cytoprotective agent against experimental ulcerations, and (3) ischemia, a predisposing factor in acute ulcerogenesis. In addition, the following studies will determine if HCO3 minus secretion is affected by secretagogues such as acetylcholine, histamine and pentagastrin and/or meditated by cGMP. The experimental model for these studies will be an in vivo canine stomach which permits the calculation of HCO3 minus secretion by measuring intragastric pCO2 and pH as described by Garner and Flemstrom. This technique will be added to our present ability to measure gastric blood flow by gamma-labeled microspheres, mucosal cGMP by radioimmunoassay and intramural pH by the microelectrode technique.